Summary
Coriander and white mustard, an annual plants originated in the Mediterranean region, have been cultivated and used as spices for a long time. Recent studies have shown that they may ...constitute a potential source of phenolic compounds. The aim of this study was to evaluate the content of polyphenols in coriander and white mustard water extracts and to investigate their antioxidant activity in C2C12 mouse skeletal muscle cells, which serve as a good model of cells with intensive metabolism. HPLC analysis showed that polyphenols were able to permeate from the water extracts of studied plants into the undifferentiated myoblasts as well as myocytes undergoing differentiation, increasing the concentration of reduced glutathione and upregulating glutathione reductase and peroxidase activity. White mustard and coriander extracts also decreased the levels of oxysterols and sum of tiobarbituric acid reactive substances (TBARS) in both: myoblasts and differentiating myocytes, demonstrating protective effect on cell membranes. The obtained results indicate that polyphenols synthesized by both herbs may have beneficial effects on muscle tissue.
Insulin-like growth factor-I is involved in mammary gland development, promoting proliferation and inhibiting apoptosis of mammary epithelial cells (MECs). Mitogenic actions of IGF-I are mainly ...mediated by the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway. We have found that in the presence of IGF-I bovine BME-UV1 MECs cultured on reconstituted basement membrane form large spheroids with disrupted polarity and no cavity in the center. These cells showed enhanced phosphorylation of Akt, decreased level of cleaved caspase-3, and sustained proliferative activity throughout the 16-d period of 3-dimensional culture. Inhibition of the PI3K/Akt pathway by a specific inhibitor of PI3K, LY294002, resulted in the restoration of the normal acinar phenotype. However, this effect was noted only when LY294002 was added in the second week of 3-dimensional culture, which corresponded with the time of cell cycle arrest and polarity formation under control conditions. Normal development of acini was also obtained when BME-UV1 cells were treated simultaneously with IGF-I and 17β-estradiol. The addition of 17β-estradiol regulated Akt activation, enabling the subsequent initiation of polarization processes. 17β-Estradiol also increased the level of IGFBP-3 protein in MECs cultured on Matrigel in the presence of IGF-I. The presented results indicate important interactions between signaling pathways activated by estrogen and IGF-I, which regulate alveologenesis in bovine mammary gland.
Natural killer (NK) cells have a unique capability of spontaneous cytotoxicity against malignant cells and hold promise for off-the-shelf cell therapy against cancer. One of the key challenges in the ...field is to improve NK cell homing to solid tumors.
To gain a deeper understanding of the cellular mechanisms regulating trafficking of NK cells into the tumor, we used high-dimensional flow cytometry, mass cytometry, and single-cell RNA-sequencing combined with functional assays, creating a comprehensive map of human NK cell migration phenotypes.
We found that the chemokine receptor repertoire of peripheral blood NK cells changes in a coordinated manner becoming progressively more diversified during NK cell differentiation and correlating tightly with the migratory response of the distinct NK cell subsets. Simultaneous ligation of CXCR1/2 and CX3CR1, synergistically potentiated the migratory response of NK cells. Analysis of 9471 solid cancers from publicly available TCGA/TARGET repositories revealed dominant chemokine patterns that varied across tumor types but with no tumor group expressing ligands for more than one chemokine receptor present on mature NK cells.
The finding that chemokine stimulation can elicit a synergistic migratory response in NK cells combined with the identified lack of naturally occurring pairs of chemokines-chemokine receptors in human cancers may explain the systematic exclusion of NK cells from the tumor microenvironment and provides a basis for engineering next-generation NK cell therapies against malignancies.
The Polish Ministry of Science and Higher Education, the National Science Centre, Poland, The Norwegian Cancer Society, the Norwegian Research Council, the South-Eastern Norway Regional Health Authority, The Swedish Cancer Society, the Swedish Children's Cancer Foundation, The Swedish Research Council, The Center of Excellence: Precision Immunotherapy Alliance, Knut and Alice Wallenberg Foundation and National Cancer Institute.
Summary
Coriander and white mustard, an annual plants originated in the
M
editerranean region, have been cultivated and used as spices for a long time. Recent studies have shown that they may ...constitute a potential source of phenolic compounds. The aim of this study was to evaluate the content of polyphenols in coriander and white mustard water extracts and to investigate their antioxidant activity in
C
2
C
12 mouse skeletal muscle cells, which serve as a good model of cells with intensive metabolism.
HPLC
analysis showed that polyphenols were able to permeate from the water extracts of studied plants into the undifferentiated myoblasts as well as myocytes undergoing differentiation, increasing the concentration of reduced glutathione and upregulating glutathione reductase and peroxidase activity. White mustard and coriander extracts also decreased the levels of oxysterols and sum of tiobarbituric acid reactive substances (
TBARS
) in both: myoblasts and differentiating myocytes, demonstrating protective effect on cell membranes. The obtained results indicate that polyphenols synthesized by both herbs may have beneficial effects on muscle tissue.
The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB.sub.1 ...and CB.sub.2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB.sub.1 and CB.sub.2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB.sub.1 and CB.sub.2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists such as JWH-133 and WIN 55,212-2 (WIN-55) in RCC cell lines. Human RCC cell lines were used for this study. The CB.sub.1 and CB.sub.2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB.sub.1 and CB.sub.2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB.sub.1 and CB.sub.2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells. The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB.sub.2 receptor as compared to CB.sub.1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB.sub.1 and CB.sub.2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB.sub.2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis. This study elucidated the involvement of CB.sub.2 in the in vitro inhibition of RCC cells, and future applications of CB.sub.2 agonists in the prevention and management of RCC are discussed.
The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB
and CB
...), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB
and CB
receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB
and CB
receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists such as JWH-133 and WIN 55,212-2 (WIN-55) in RCC cell lines.
Human RCC cell lines were used for this study. The CB
and CB
gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB
and CB
receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB
and CB
receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells.
The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB
receptor as compared to CB
in RCC cells. Immunocytochemical staining also confirmed the expression of the CB
and CB
proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB
agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis.
This study elucidated the involvement of CB
in the in vitro inhibition of RCC cells, and future applications of CB
agonists in the prevention and management of RCC are discussed.
PDF